The current standard for detecting and monitoring progression of diseases of the optic nerve (i.e. glaucoma, ischemic optic neuropathy, compressive optic neuropathy) and retina is visual field testing (perimetry). Perimetry is a functional test of the patient's vision. The shape and extent of the defect on the visual field map allows the clinician to confirm the presence of damage, helps to determine damage location along the visual pathway (retina, optic nerve, chiasm, optic tract, postgeniculate fibers), and is essential in monitoring progression or improvement over time.
Perimetry remains a subjective test that requires the patient to make important judgments and reports during the test that can be clouded by anxiety, fatigue, or lack of concentration. Also, a high percentage (approximately 40–50%) of the optic nerve may be damaged before a significant perceptual change can be detected on the visual field test, making perimetry relatively insensitive for detecting early damage when intervention may still save vision. Further, the visual field test is highly variable in areas of defects where damage has occurred, making it difficult to monitor changes.
Direct measurement of neuronal activity avoids the subjective nature of perimetry techniques, which require interactive perception reports from the patient. Traditionally, neuronal activity in the central nervous system including the retina has been recorded electrically. Recently however, noninvasive optical recording of neuronal signals from the brain has become possible. Intrinsic changes in the optical properties of active brain tissue (referred to as “intrinsic signals”) permit visualization of neuronal activity when the surface of brain tissue is directly imaged using sensitive CCD cameras. Intrinsic signals refer to the fluctuations in the reflectance properties of tissue illuminated (or interrogated) by light. Such fluctuations result from changes in the absorption coefficient of the interrogated tissue due to the conversion of oxyhemoglobin to deoxyhemoglobin in response to the metabolic demands of active neurons. The interrogating light is band-restricted to wavelength(s) where the difference in absorption spectra between the oxyhemoglobin and deoxyhemoglobin molecule is the greatest, typically in the region of 580–700 nanometers (nm). Other sources of the intrinsic signals include changes in the microcirculation and light scattering, which are also dependent on neuronal activity.
The intrinsic signals from the brain are usually very small (0.1 to 1.0% of the overall reflected light intensity). However, when appropriately imaged, they can have high spatial resolution (50 microns) corresponding to the areas of active neuronal activity. The small intrinsic signals are isolated from noise using image subtraction or ratio techniques. By subtracting baseline (neuronally less active) images of the brain tissue from stimulated (neuronally active) images, (or taking the ratio of the images), small intrinsic functional signals can be isolated. With the use of optical techniques, it has been possible to record neuronal activities of the primate cortex in vivo. Perhaps the best example of optical recording of intrinsic signals in brain tissue has been the visualization of ocular dominance columns in the monkey primary visual cortex.
Visual cortical neurons that are driven preferentially by one eye are grouped into a strip of the cortex referred to as an ocular dominance column for the associated eye. Typically, an adjacent strip of cortical cells is driven preferentially by the other eye and forms an adjoining ocular dominance column. Strips of ocular dominance columns alternate between the right and left eye and form a prominent part of the functional architecture of the primate visual cortex. Ocular dominance columns were originally discovered through painstaking reconstruction of the locations and electrical responses of hundreds of individually recorded neurons. The optical recording of intrinsic signals has allowed the ocular dominance columns to be directly visualized across the cortex in vivo. This was achieved by imaging the cortex with interrogating light, while providing visual stimuli to one eye and then the other. Ocular dominance column images were then constructed by subtracting right eye-stimulated images from the left eye-stimulated images. Optical recording of the temporal lobe of human patients undergoing neurosurgery has also been reported.
New objective methods are needed to improve the sensitivity for detection of damage to the retina and optic nerve and change over time. Such methods would also provide more reliable determination of the status of the visual system. A number of new technologies have emerged in recent years in an attempt to fill this need and have included multifocal electroretinography (MERG) pattern electroretinography (PERG), visual evoked potential (VEP), multifocal visual evoked potentials (MVEP), and pupil perimetry.
A practical, highly sensitive and specific device for revealing retinal function is needed to aid in early detection of retinal and optic nerve diseases such as glaucoma and to monitor the progression of neuronal damage. This need is driven by the fact that standard glaucoma therapy of lowering intraocular pressure can reduce the rate of further optic disc damage. In addition, it would also be advantageous to be able to image the stimulus-associated activity of other layers of the retina, such as the deeper layers containing bipolar cells, photoreceptors and pigmented epithelium to assess the health of these layers in other diseases of the eye. It is these observations that have motivated the development a new functional imaging technique for the eye that would reveal activation of regions of the retina in response to visual stimuli.